Role of Ring Finger Protein 213 in Moyamoya Disease

The aim of this study was to help people comprehensively understand the research advances related to ring finger protein 213 (RNF213) in moyamoya disease (MMD) and to understand the disease at the molecular level to provide a new perspective of the diagnosis of the disease.

This review was based on data in articles published between 2005 and 2015 that were retrieved from the PubMed database. The search terms included RNF213, MMD, intracranial major artery stenosis /occlusion (ICASO), genotype, phenotype, mutant and variants, and the combinations of these terms.

Articles related to MMD and RNF213 were selected for review, and we also reviewed publications related to ICASO.

RNF213 is not only associated with MMD but also associated with intracranial major artery stenosis. In addition, RNF213 variants exhibit apparent ethnic diversity; specifically, the c.14576G>A variant is mainly detected in Korean, Chinese, and Japanese populations, particularly the latter population. The genotypes of RNF213 correlate with the phenotypes of MMD; for example, the homozygous c.14576G>A variant is associated with early-onset, severe symptoms, and an unfavorable prognosis. Furthermore, the RNF213 c.14576G>A variant should be considered during the diagnosis of MMD because no patients with quasi-MMD have been reported to carry the RNF213 c.14576G>A variant whereas 66 of 78 patients with definite MMD have been found to carry this variant.

The growing literature demonstrates that MMD is primarily caused by the synergy of genetic and environmental factors, and unknown genetic modifiers might play roles in the etiology of MMD. Further research should be conducted to clarify the pathogenic mechanism of MMD.